Obituaries / Joshua Lederberg, 1925 - 2008

Nobel Prize winner was genetics pioneer

Joshua Lederberg, who won a Nobel Prize for discovering that bacteria could have sex, thereby establishing the foundation of modern genetics and biotechnology, died of pneumonia Saturday in New York City. He was 82.

The prodigy's pioneering work while he was still in graduate school made him one of the first researchers to manipulate genes in a living organism. It opened the door to an understanding of how bacteria evolved and the mechanisms by which they develop and transfer antibiotic resistance.

It also set the stage for a long and fruitful career in space biology and artificial intelligence, as well as four decades on government advisory commissions on health policy, national security and arms control.

As president of Rockefeller University in New York City from 1978 to 1990, he was instrumental in the renovation of many of the scientific research institution's facilities and the construction of new ones.

"Josh was one of the most creative scientists of our times," said molecular biologist Stanley N. Cohen of Stanford University. "He thought more broadly and more deeply about more things than anyone I've ever known. His death is a loss to all of us."

When Lederberg began his research immediately after World War II, biologists had a very limited understanding of genetics and bacterial reproduction. Pioneering molecular biologist Oswald Avery had discovered in 1944 that deoxyribonucleic acid, or DNA, was the material that encoded the genetic information of life, including bacteria.

Inspired by the findings, Lederberg took a leave of absence from Columbia University medical school and began studying pneumococci and Escherichia coli with Edward L. Tatum of Yale University. At the time, bacteria were thought to be simple organisms that reproduced by cell division and thus produced offspring that were genetically identical to the parent -- that is, clones.

Within a year, the pair were able to show that E. coli underwent a sexual stage in which it could mate and exchange genetic information, a process called recombination or conjugation. When bacteria in the sexual stage came into contact, they could exchange rings of DNA -- separate from their nuclear DNA -- that Lederberg dubbed plasmids.

That nomenclature did not catch on until the 1970s, however, when it became clear that genes encoded in the plasmids were the mechanism by which bacteria transferred antibiotic resistance from one organism to another.

In 1952, working with his student Norton D. Zinder, Lederberg identified a second mechanism for exchange of genes, called transduction. In transduction, viruses that infect bacteria remove one or more genes from the DNA of a bacterium and insert it into the genome of a second one.

That finding was the first demonstration of the manipulation of an organism's genetic material and ultimately served as the basis for the techniques of genetic engineering.

In 1958, at the age of 33, Lederberg was awarded half of the Nobel Prize in Physiology or Medicine. The other half was shared by Tatum and George Beadle, who were honored for their discovery in the 1940s that genes acted by regulating specific chemical processes.

The fame conferred by the Nobel Prize allowed Lederberg to expand his interests. Following the launch of Sputnik in 1958, he began arguing that biologists should have a place in the exploration of space, coining the term "exobiology" to refer to the study of life outside Earth.

With physicist Dean B. Cowle, he argued that astronauts and spacecraft returning to Earth should be quarantined to prevent a potentially catastrophic infection by extraterrestrial germs. They also argued that our own spacecraft be sterilized before launch to prevent the possible contamination of biological life on other planets. Both suggestions were adopted.

Lederberg helped design and build automated instruments to detect signs of life on Mars as part of NASA's 1975 Viking mission. That, in turn, led him to advocate expanding the role of computers in science. He and Edward Feigenbaum of Stanford University developed a computer program called DENDRAL, designed to help identify unknown chemical compounds from spectroscopic and laboratory data. It was the first expert system for use in science.

Among his many government advisory positions, he served as a consultant to the Arms Control and Disarmament Agency during the negotiation of the biological weapons disarmament treaty.

In his later years, he spoke often about the threat to humankind from the potential emergence of multi-drug-resistant microorganisms.

Among the many honors he received for his achievements were the National Medal of Science in 1998 and the Presidential Medal of Freedom in 2006, the nation's highest civilian award.